Characterization of gastrointestinal changes in a mouse model of Parkinson’s disease

Parkinson’s disease is a neurodegenerative disorder that results in the death of dopaminergic neurons. The death of dopaminergic neurons results in motor deficits of which bradykinesia, resting tremor, and rigidity are the principal symptoms. In addition to the motor symptoms, PD patients often experience disturbances to their gastrointestinal systems. These symptoms often appear years before the motor symptom debut. Studies have shown alterations in the microbiota of PD patients. To study PD pathology, our lab has developed a transgenic mouse model that expresses human a-Syn under the control of the mouse’s endogenous promoter. To study whether the mice reflected the gastrointestinal pathology of PD, stool samples from the transgenic and... (More)

Parkinson’s disease is a neurodegenerative disorder that results in the death of dopaminergic neurons. The death of dopaminergic neurons results in motor deficits of which bradykinesia, resting tremor, and rigidity are the principal symptoms. In addition to the motor symptoms, PD patients often experience disturbances to their gastrointestinal systems. These symptoms often appear years before the motor symptom debut. Studies have shown alterations in the microbiota of PD patients. To study PD pathology, our lab has developed a transgenic mouse model that expresses human a-Syn under the control of the mouse’s endogenous promoter. To study whether the mice reflected the gastrointestinal pathology of PD, stool samples from the transgenic and wildtype mice were compared for the following bacteria: Akkermansia muciniphila, Escherichia coli, Fecalibacterium prausnitzii, Enterobacteriaceae, and Verrucomicrobiacea. These bacteria and bacterial families have previously been shown to be affected in inflammatory bowel disturbances. The transgenic mice showed significant loss of A. muciniphila in their feces compared to the wildtypes. Additionally, the transgenic mice exhibited lower percentages of water in their stools, a measure of constipation. The discovery of one group of transgenic mice positive for A. muciniphila led to the study of motor behavior between the two groups of transgenic mice: those with or without A. muciniphila in their feces. Surprisingly, differences indicating a worsening of the phenotype for the transgnic mice with A. muciniphila in their feces could be seen in both the rotarod and openfield assays. To examine whether similar microbiota differences could be seen in human samples, stool samples from PD patients and healthy controls were compared for the aforementioned bacteria. No significant changes could be seen for any of the bacteria. To test whether alpha synuclein (a-Syn) in feces could be used as a biomarker for PD, Western Blots with PD and control stool samples were analyzed with an a-Syn-detecting antibody. Stainings could be seen for the PD samples but not in the controls. To test whether a-Syn had any inhibitory effects on the growth of A. muciniphila and E. coli, the two bacteria were cultured and a-Syn added to the plates. No effect of a-Syn could be seen on the growth and survival of either strain. Although A. muciniphila might not play a causative role in PD pathology, there seems to be a correlation with its presence in feces and disease phenotype. (Less)

@misc{8893017,
abstract = {Parkinson’s disease is a neurodegenerative disorder that results in the death of dopaminergic neurons. The death of dopaminergic neurons results in motor deficits of which bradykinesia, resting tremor, and rigidity are the principal symptoms. In addition to the motor symptoms, PD patients often experience disturbances to their gastrointestinal systems. These symptoms often appear years before the motor symptom debut. Studies have shown alterations in the microbiota of PD patients. To study PD pathology, our lab has developed a transgenic mouse model that expresses human a-Syn under the control of the mouse’s endogenous promoter. To study whether the mice reflected the gastrointestinal pathology of PD, stool samples from the transgenic and wildtype mice were compared for the following bacteria: Akkermansia muciniphila, Escherichia coli, Fecalibacterium prausnitzii, Enterobacteriaceae, and Verrucomicrobiacea. These bacteria and bacterial families have previously been shown to be affected in inflammatory bowel disturbances. The transgenic mice showed significant loss of A. muciniphila in their feces compared to the wildtypes. Additionally, the transgenic mice exhibited lower percentages of water in their stools, a measure of constipation. The discovery of one group of transgenic mice positive for A. muciniphila led to the study of motor behavior between the two groups of transgenic mice: those with or without A. muciniphila in their feces. Surprisingly, differences indicating a worsening of the phenotype for the transgnic mice with A. muciniphila in their feces could be seen in both the rotarod and openfield assays. To examine whether similar microbiota differences could be seen in human samples, stool samples from PD patients and healthy controls were compared for the aforementioned bacteria. No significant changes could be seen for any of the bacteria. To test whether alpha synuclein (a-Syn) in feces could be used as a biomarker for PD, Western Blots with PD and control stool samples were analyzed with an a-Syn-detecting antibody. Stainings could be seen for the PD samples but not in the controls. To test whether a-Syn had any inhibitory effects on the growth of A. muciniphila and E. coli, the two bacteria were cultured and a-Syn added to the plates. No effect of a-Syn could be seen on the growth and survival of either strain. Although A. muciniphila might not play a causative role in PD pathology, there seems to be a correlation with its presence in feces and disease phenotype.},
author = {Haikal, Caroline},
language = {eng},
note = {Student Paper},
title = {Characterization of gastrointestinal changes in a mouse model of Parkinson’s disease},
year = {2016},
}